Pancreas is an organ located behind the stomach. It secretes a variety of digestive enzymes which promote degradation of the carbohydrates, proteins and fats that passed through the stomach. Also, it produces important hormones such as insulin, glucagon and the like. If the secretion of digestive enzymes from the pancreas is insufficient, the uptake of nutrients becomes insufficient. In addition, the secretion of insulin and glucagon regulates intravascular glucose levels. Studies on the mechanisms that control the production and secretion of these various enzymes and hormones have become important topics in relation to nutrition and diverse diseases, such as diabetes, obesity and the like.
Major diseases that occur in relation to the pancreas include pancreatic cancer, pancreatitis, diabetes and the like. Diabetes is a risky disease that occurs when insulin secretion in the pancreas declines or resistance to insulin action in other tissues occurs, leading to various complications due to elevated blood glucose levels. In addition, pancreatic cancer is known to be a disease that has the highest mortality rate among malignant tumors and has a poor prognosis.
The most common treatment methods for the treatment of diseases related to the pancreas are performed by the administration or intravenous infusion of analgesics, antibiotics, anticancer drugs, or the like. In severe cases, pancreaticoduodenectomy is performed, which treats the diseases by surgery.
The pancreaticoduodenectomy has been widely distributed by Whipple et al. since successful pancreaticoduodenectomy was first introduced by Kausch in 1912. The pancreaticoduodenectomy is an important surgical procedure that is applied to radical treatment of Vater periampullary cancer which occurs in the pancreas, head, common bile duct, duodenal ampulla or the like, but it is a surgical method having a high possibility of developing postoperative complications. Until the 1970s, the pancreaticoduodenectomy was reported to have a postoperative mortality rate of about 20%. Recently, pancreaticoduodenectomy has been reported to have a mortality rate of 5% or less due to advances in surgical technology, anesthetic technology, patient management before and after surgery, nutritional management, and the like.
However, despite the dramatic decrease in mortality rate, the incidence of postoperative complications has been reported to be 40-50% even in recent years. Among these complications, the incidence of pancreatic leakage, which is closely related to mortality rate, has been reported to be still 10-20%. It was found that pancreatic leakage, when occurred, could cause intraperitoneal hemorrhage, abscess or the resulting sepsis, and the mortality rate associated with it was also high.
According to several reports, it is known that the diameter of the pancreatic duct, the consistency of the pancreatic parenchyma, and the like, are risk factors that are involved in the occurrence of pancreatic leakage. Here, regarding the consistency of the pancreatic parenchyma, the pancreas parenchyma remaining after pancreatectomy is very soft, so there is a high risk of crushing the tissue at the time of suturing, and hence a high level of skill is required for suturing. Even after the suturing, anastomosis is not properly achieved, so that pancreatic juice flows out through the gap, causing the pancreatic leakage.
Accordingly, recently, pancreas-jejunum anastomosis, pancreas-stomach anastomosis, pancreatic duct-mucosal anastomosis, dunking, stent implantation and the like have been proposed to prevent the occurrence of postoperative pancreatic leakage. In addition to these surgical suturing methods, somatostatin, fibrin glue or the like has also been proposed.
The present inventors have found that novel compounds synthesized using the structure of existing antibiotics as a basic skeleton can temporarily harden the pancreas, and thus can increase the efficiency of suturing during pancreatic surgery such as pancreaticoduodenectomy, thereby completing the present invention.